Haemostatic Profiles are Similar across All Aetiologies of Cirrhosis

Abstract

Background and Aim Patients with cirrhosis may acquire profound changes in haemostasis. Although haemostatic changes in cirrhosis have been extensively studied, most studies were performed in groups of patients with mixed aetiology. As thrombotic events appear more common in some aetiologies of disease, notably non-alcoholic steatohepatitis (NASH) and cholestatic disease, we hypothesized that haemostatic changes might be different across aetiologies. Patients and Methods We studied 109 patients with cirrhosis (31 cholestatic liver disease, 23 NASH, 37 alcoholic liver disease [ALD], 18 viral hepatitis) and 44 healthy controls. Patients with malignancy were excluded. Routine diagnostic tests of haemostasis, thrombin generation assays, fibrin permeability assays and a plasma-based fibrinolytic assay were performed. Results All patients had comparable severity of disease according to their Model for End-Stage Liver Disease score (9 [7–11]). Plasma levels of von Willebrand factor were substantially elevated across all aetiologies, with a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 levels comparable to controls. Thrombin generation capacity was elevated in all aetiologies, most profoundly in ALD. Fibrin permeability was decreased in all aetiologies, which was accompanied by elevated fibrinogen levels. Clot lysis times were prolonged in NASH and cholestatic disease. Plasma levels of individual proteins were similarly altered in all aetiologies. Conclusion Our in-depth haemostatic profiling of primary, secondary and tertiary haemostasis in a group of patients with Childs–Turcotte–Pugh A/B cirrhosis showed no large differences between aetiologies, and was consistent with a general hypercoagulable profile in patients with mild cirrhosis. These results suggest that patients with cirrhosis have an increased risk of thrombosis, irrespective of their aetiology.

Whole blood thrombin generation profiles of patients with cirrhosis explored with a near patient assay

“…Using the near patient WB‐TG assay, we observed that the endogenous thrombin generating potential (ETPp) values of patients with cirrhosis, regardless of the presence/absence of TM, were in the same range as in healthy controls, suggesting that these patients had normal thrombin‐generating capacity. The standard PPP‐TG results add to the growing literature that hypocoagulable state is suggested when TG is tested without activating the protein C pathway, whereas hypercoagulable state is found when the function of the anticoagulant protein C pathway is included in TG by adding TM into the test . These results indicate that cirrhosis does not necessarily result in a hypocoagulable state as suggested by their lower procoagulant factor levels and prolonged PT and APTT, thus reinforcing that prophylactic administration of fresh‐frozen plasma according to their PT/APTT is not required …”

“…Abbreviations: ETPp, endogenous thrombin potential until the thrombin peak; TG, thrombin generation; TM, thrombomodulin; TTP, time to peak; WB, whole blood TA B L E 2 Whole blood thrombin generation profiles of patients and controls the anticoagulant protein C pathway is included in TG by adding TM into the test. 6,[24][25][26][27]30 These results indicate that cirrhosis does not necessarily result in a hypocoagulable state as suggested by their lower procoagulant factor levels and prolonged PT and APTT, thus reinforcing that prophylactic administration of fresh-frozen plasma according to their PT/APTT is not required. 31,32 Of note, although the TG capacity of cirrhotic patients is comparable to the controls, their peak thrombin level is discordantly lower, suggesting a hypocoagulable state.…”

“…TG assays have been extensively used to study the coagulation profiles of patients with liver disease, and studies using TM-modified plasma TG assay have shown intact or elevated TG potential in cirrhosis, supporting the concept that these patients have re-balanced hemostasis. 6,[23][24][25][26][27] However, until now all studies on TG profiles in these patients were performed in plasma samples, which has limitations, such as the requirement for a specialized laboratory environment, a longer turnaround time for results, and the inability to study the effect of most blood cells (except platelets) on TG. Until now there are no published data of WB-TG measurements in liver disease patients.…”

Hemostatic Alterations in Patients With Cirrhosis: From Primary Hemostasis to Fibrinolysis

“…No differences were noted in donors with alcohol-associated/viral LC versus donors who were healthy. (55) Additionally, decreased ADAMTS13 activity can also be secondary to increased VWF. (56) In sum, decreased ADAMTS13 activity, leading to enhanced VWF:Ac, could be a mechanism compensating thrombocytopenia.…”

Mixed Fibrinolytic Phenotypes in Decompensated Cirrhosis and Acute‐on‐Chronic Liver Failure with Hypofibrinolysis in Those With Complications and Poor Survival

“…The net effect of these changes is a hemostatic system that is in a “rebalanced” status, although notable hyper‐ and hypocoagulable features may be present . Although there is increasing consensus that a decreased platelet count in patients with cirrhosis is (in part) balanced by highly elevated plasma levels of von Willebrand factor and that the thrombin‐generating capacity is normal to increased compared with healthy individuals, there is continuing controversy on the status of the fibrinolytic system . Using various approaches, it has been demonstrated that some patients with cirrhosis are in a hyperfibrinolytic state, which is ascribed to complex changes in plasma levels of fibrinolytic proteins, with an important role for elevated levels of tissue‐type plasminogen activator (tPA) .…”